The prior art processes for the preparation of l-biopterin include:
(1) Reaction of 4-hydroxy-2,5,6-triaminopyrimidine (TAP) and 5-deoxy-L-arabinose in accordance with the following reaction formula ##STR1## (E. L. Patterson et al., J. Am. Chem. Soc., 78, 5868 (1956)),
(2) Reaction of TAP and 5-deoxy-L-arabinose phenylhydrazone in accordance with the following reaction formula ##STR2## (Matsuura et al., Bull. Chem. Soc. Jpn., 48, 3767 (1975)),
(3) Reaction of TAP and triacetyloxy-5-deoxy-L-arabinose phenylhydrazone in accordance with the following reaction formula ##STR3## (M. Viscontini et al., Helv. Chim. Acta., 60, 211 (1977)),
(4) Reaction of oxime and benzyl .alpha.-aminocyanoacetate in accordance with the following reaction formula ##STR4## and condensation of the resulting 3-(1,2-dihydroxypropyl)-pyrazine-1-oxide derivatives with guanidine followed by deoxygenation of the N-oxide (E. C. Taylor et al., J. Am. Chem. Soc., 96, 6781 (1974)),
(5) Reaction of .alpha.-hydroxyketone (prepared from crotonic acid) and TAP in accordance with the following reaction formula ##STR5## (M. Viscontini et al., Helv. Chim. Acta., 55, 574 (1972)) and
(6) Reaction of TAP having protected hydroxyl group and 4-acetoxy-2,3-epoxypentanal in accordance with the following reaction formula ##STR6## followed by oxidation with iodine and deprotection (Matsuura et al., Chemistry of Organic Synthesis, Vol. 46, No. 6, p. 570 (1988)).
The prior processes (1) to (4) starting from 5-deoxy-L-arabinose are not economically advantageous, since 5-deoxy-L-arabinose is difficult to be available industrially in large quantities and it is prepared starting from expensive L-rhamnose followed by subjecting to known degradation in sugar chemistry.
The prior processes (5) and (6) are not started from L-rhamnose but have the disadvantages in that biopterin is produced in a dl-form and optical resolution is required for obtaining the desired l-biopterin, thus leading to complicated process step and low yield.
Thus there has been demanded a process for the preparation of l-biopterin in good yield using inexpensive starting material.
In view of the above matters, we have proposed a process for the preparation of l-biopterin starting from (S)-alkyl lactate as disclosed in Japanese Kokai No. 221380/1989. That process comprises protecting the hydroxyl group of S-alkyl lactate with a trityl group, reducing a resulting alkyl 2-trityloxypropionate to (S)-2-trityloxypropanol, oxidizing it to (S)-2-trityloxypropanal, treating it with a 2-furyl metal compound to form (1S, 2S)-1-(2-furyl)-2-trityloxy-1-propanal followed by oxidation and hydrolysis to form 2,3-dideoxy-6-trityloxyhepto-2-enopyranose-4-ulose, reducing it to 6-trityloxyhepto-2-ene-1,4,5-triol, acylating it to from 1,4,5-triacyloxy-6-trityloxyhepto-2-ene followed by oxidation to afford 2,3 diacyloxy-4-hydroxy-1-pentanal, treating it with phenylhydrazine to from a hydrazine, and condensing the hydrazine with a 3,5,6-triaminopyrimidinol followed by oxidation and deacylation.